Engagement of sialylated glycans with Siglec receptors on suppressive myeloid cells inhibits anticancer immunity via CCL2  

作　　者：Ronja Wieboldt Michael Sandholzer Emanuele Carlini Chia-wei Lin Anastasiya Börsch Andreas Zingg Didier Lardinois Petra Herzig Leyla Don Alfred Zippelius Heinz Läubli Natalia Rodrigues Mantuano 

机构地区：[1]Laboratory for Cancer Immunotherapy,Department of Biomedicine,University Hospital and University of Basel,Basel,Switzerland. [2]Functional Genomics Center Zurich,ETH Zurich,Zurich,Switzerland. [3]Bioinformatics Core Facility,Department of Biomedicine,University of Basel and Swiss Institute of Bioinformatics,Basel,Switzerland. [4]Department of Thoracic Surgery,University Hospital Basel,Basel,Switzerland. [5]Laboratory of Cancer Immunology,Department of Biomedicine,University Hospital and University of Basel,Basel,Switzerland. [6]Division of Oncology,University Hospital Basel,Basel,Switzerland.

出　　处：《Cellular & Molecular Immunology》2024年第5期495-509,共15页中国免疫学杂志（英文版）

基　　金：supported by funding from the Swiss National Science Foundation(SNSF Grant No.310030-215237/1);the Schoenmakers-Müller Foundation,a research grant from Ono Pharmaceuticals,and the Cancer League of Basel(KlbB).Open access funding provided by University of Basel.

摘　　要：The overexpression of sialic acids on glycans,called hypersialylation,is a common alteration found in cancer cells.Sialylated glycans can enhance immune evasion by interacting with sialic acid-binding immunoglobulin-like lectin(Siglec)receptors on tumorinfiltrating immune cells.Here,we investigated the effect of sialylated glycans and their interaction with Siglec receptors on myeloid-derived suppressor cells(MDSCs).We found that MDSCs derived from the blood of lung cancer patients and tumor-bearing mice strongly express inhibitory Siglec receptors and are highly sialylated.In murine cancer models of emergency myelopoiesis,Siglec-E knockout in myeloid cells resulted in prolonged survival and increased tumor infiltration of activated T cells.Targeting suppressive myeloid cells by blocking Siglec receptors or desialylation strongly reduced their suppressive potential.We further identified CCL2 as a mediator involved in T-cell suppression upon interaction between sialoglycans and Siglec receptors on MDSCs.Our results demonstrated that sialylated glycans inhibit anticancer immunity by modulating CCL2 expression.

关 键 词：sialoglycans Sialic acid-binding immunoglobulin-like lectin tumor microenvironment myeloid derived suppressor cells 

分 类 号：R730.51[医药卫生—肿瘤]